Simian Immunodeficiency Virus Infects Functionally Polarized Memory CD4 T Cells Equivalently In Vivo

Abstract

Among the numerous immunological abnormalities observed in chronically human immunodeficiency virus (HIV)-infected individuals, perturbations in memory CD4 T cells are thought to contribute specifically to disease pathogenesis. Among these, functional imbalances in the frequencies of T regulatory cells (Tregs) and interleukin 17 (IL-17)/IL-22-producing Th cells (Th17/Th22) from mucosal sites and T follicular helper (Tfh) cells in lymph nodes are thought to facilitate specific aspects of disease pathogenesis. However, while preferential infection of Tfh cells is widely thought to create an important viral reservoir in an immunologically privileged site in vivo, whether immunological perturbations among memory CD4 T cell populations are attributable to their relative infectivity by the virus in vivo is unclear.Here we studied peripheral blood and lymphoid tissues from antiretroviral (ARV)treated and ARV-naive Asian macaques and isolated functionally defined populations of memory CD4 T cells. We then assessed the degree to which these populations were infected by simian immunodeficiency virus (SIV) in vivo, to determine whether particular functionally identified populations of memory CD4 T cells were preferentially infected by the virus. We found that SIV did not preferentially infect Th17 cells, compared to Th1 cells, Th2 cells, or Tregs. Moreover, Th17 cells contributed proportionately to the total pool of infected cells. Taken together, our data suggest that, although Tfh cells are more prone to harbor viral DNA, other functionally polarized cells are equally infected by the virus in vivo and Th17 cells are not preferentially infected. IMPORTANCE Functional perturbations of memory CD4 T cells have been suggested to underlie important aspects of HIV disease progression. However, the mechanisms underlying these perturbations remain unclear. Using a nonhuman primate model of HIV, we show that SIV infects functionally defined populations of memory CD4 T cells equally in different anatomic sites. Thus, preferential infection by the virus is unlikely to cause functional perturbations.

Th17 CD4+ T-Cell as a Preferential Target for HIV Reservoirs

“…Compared to Th1 and Th2 oriented CD4 T cells, Th17 cells show a superior permissivity and the highest level of HIV DNA integration in vitro and in vivo (12,39). In contrast, during SIV (simian immunodeficiency virus) infection of rhesus macaques, Th17 cells are not preferentially infected compared to CD4+ memory T cells (70). These data suggest a limitation of using the SIV model to study differences in infectivity between Th17 cells and other CD4+ T cells.…”

FRugally Optimized DNA Octomer (FRODO) qPCR Measurement of HIV and SIV in Human and Nonhuman Primate Samples

“…This technique can be used to enumerate numbers of viruses, bacterial taxa, and immunological genes of interest in biological samples from in vitro and ex vivo experiments. This approach is used to determine the numbers of HIV or SIV DNA copies per cell of interest after viral infection both in vitro and in vivo (Beaumier et al., 2009; Brenchley et al., 2004; Chomont et al., 2009; Lai et al., 2019; Mattapallil et al., 2005). These experiments involve measuring quantities of viral DNA relative to the number of host cells, determined by copy numbers of targeted host genes, via qPCR.…”